UMLS:C0027819 - FACTA Search

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Query: UMLS:C0027819 (neuroblastoma)
27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Children with malignancies resistant to conventional therapy were treated with cis-diamminedichloroplatinum (PDD), 15 to 20 mg/m2, given daily by rapid intravenous infusion for 5 days at 3-wk intervals. Eleven of 24 children with acute lymphocytic leukemia (ALL) received two or more courses; among these no remissions occurred. Fifty-four children with solid tumors were treated: 25 neuroblastoma, 9 rhabdomyosarcoma, 4 Ewing sarcoma, 2 testicular embryonal carcinoma, 2 retinoblastoma, and 12 miscellaneous tumors. One complete remission, 3 partial remissions, and 2 improvements were observed in children with neuroblastoma. One girl with metastatic osteogenic sarcoma achieved a partial remission. One child with metastatic testicular embryonal carcinoma showed improvement. The side effects were vomiting controlled by antiemetics in 26 children and transient elevations of serum creatinine and BUN in 14 children. Nineteen of 39 children with solid tumors, who received more than one course of PDD, had moderately severe myelosuppression caused by PDD. In summary, PDD is a promising agent in neuroblastoma, osteogenic sarcoma, and testicular embryonal carcinoma, and an ineffective agent in ALL. The effect of PDD on other types of solid tumors should be evaluated in the future.
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PMID:Cis-diamminedichloroplatinum (NSC-119875) in childhood malignancies: a Southwest Oncology Group study. 27 32

Glioblastomas are among the most malignant tumours for which no curative treatment exists. A dysfunction of cellular immunity with decreased skin reactivity and lymphocyte blastogenesis has been described in patients with glioblastomas. In culture human glioblastoma cells release a factor termed glioblastoma-derived T cell suppressor factor (G-TsF) which inhibits the antigen-dependent growth of both helper and cytotoxic T cells. Purification and cloning indicated that G-TsF is a novel member of the TGF-beta family with a well-conserved mature sequence but less homology in the precursor segments. The factor was renamed TGF-beta 2. The two glioblastoma cell lines investigated expressed mRNAs for both G-TsF/TGF-beta 2 and TGF-beta 1 but only G-TsF/TGF-beta 2 protein was secreted. Neuroblastoma cells express only the mRNA for TGF-beta 1 but not the protein, nor the mRNA for G-TsF/TGF-beta 2. Recombinant G-TsF/TGF-beta 2 inhibits the generation of virus-specific cytotoxic T cells when injected into mice infected with lymphocytic choriomeningitis virus. Thus G-TsF/TGF-beta 2 might contribute to the impairment of tumour immune surveillance. Some T cell clones may escape the immunosuppressive effects of TGF-beta: ovalbumin-specific T helper cell lines that showed different degrees of susceptibility to TGF-beta contained clones which had lost receptor(s) for TGF-beta.
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PMID:Expression of TGF-beta 2 in human glioblastoma: a role in resistance to immune rejection? 164 35

Transforming growth factor (TGF)-beta 1 is a polypeptide that is assumed to play a fundamental role in the growth of both normal and neoplastic cells. TGF-beta 2 is a closely related polypeptide, originally described as glioblastoma cell-derived T cell suppressor factor (G-TsF) due to its immunosuppressive activity. Expression of the genes for TGF-beta 1 and G-TsF/TGF-beta 2 was examined in tumor cells and was found to be different in several cell lines and tissues that were tested. Whereas two glioblastoma cell lines expressed both TGF-beta 1 and G-TsF/TGF-beta 2 mRNA, one melanoma and neuroblastoma cell lines showed only TGF-beta 1 mRNA which in the case of the neuroblastoma required cycloheximide treatment for its detection. The coordinate expression of the genes for TGF-beta 1 and G-TsF/TGF-beta 2 in glioblastoma was not paralleled by secretion of both polypeptides as only G-TsF/TGF-beta 2 but not TGF-beta 1 was identified in supernatants of glioblastoma cells. These data provide evidence for a post-transcriptional level of regulation for production of the two forms of TGF-beta. As mRNA for G-TsF/TGF-beta 2 was also identified in fresh surgically removed human glioblastoma tissue, G-TsF/TGF-beta 2 may also be secreted within the tumor in vivo. Unlike glioblastoma, human fetal brain tissues or adult brain specimens studied did not express detectable levels of TGF-beta mRNA. Impaired cell-mediated immunity is an established finding in patients with glioblastoma. Secretion of G-TsF/TGF-beta 2 by tumor cells in vivo may contribute to decreased immune surveillance for tumor development, as well as neovascularization of the tumor tissue.
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PMID:Immunosuppression and transforming growth factor-beta in glioblastoma. Preferential production of transforming growth factor-beta 2. 280 98

Many recent reports have indicated that the effect of the phorbol ester tumor promoters is mediated through the Ca2+/phospholipid dependent protein kinase C. We have investigated the effect of two biologically active phorbol esters, 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) and 4 beta-phorbol 12 beta,13 alpha-didecanoate (beta PDD) on muscarinic agonist binding and receptor-stimulated phosphoinositide breakdown in cultured human neuroblastoma (SH-SY5Y) cells. Preincubation of these cells with phorbol esters significantly reduced the carbachol-stimulated breakdown of inositol phospholipids and caused a decrease of agonist affinity for [3H](-)methyl quinuclidinyl benzilate ([3H](-)MQNB) binding without affecting the affinity of antagonist to the muscarinic receptor. The nontumor promoting 4 alpha-phorbol 12 beta,12 alpha-didecanoate (alpha PDD) was ineffective in our studies. These results suggest that the activation of protein kinase C may play an important role in regulating the muscarinic receptor system.
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PMID:Phorbol esters alter muscarinic receptor binding and inhibit polyphosphoinositide breakdown in human neuroblastoma (SH-SY5Y) cells. 302 14

The effect of some anticancer agents that produce toxic effects on electrically excitable cells in vivo was studied in vitro with the use of differentiated N1E-115 murine neuroblastoma cells and single microelectrode electrical recording. In the presence of 10(-7) g/ml tetrodotoxin, following the release of 500-millisecond conditioning hyperpolarization, the cells exhibited Ca2+-dependent action potentials. Local application to N1E-115 neuroblastoma cells of cisplatin (cis-PDD) for 30 seconds from a drug-containing effusion pipette produced a dose-dependent reversible inhibition of the Ca2+-dependent action potential, with a 61% inhibition at 1.7 microM and 67% inhibition at 17 microM cis-PDD. trans-Dichlorodiammineplatinum(II) and platinic(IV) chloride, both of which lacked the growth inhibitory properties of cis-PDD against N1E-115 neuroblastoma cells, at concentrations of 170 and 120 microM produced only an 11 and 19% inhibition of the Ca2+-dependent action potential, respectively. Vincristine at a concentration of 1 microM reversibly inhibited the Ca2+-dependent action potential by 48%. 3'-Deamino-3'-(3''-cyano-4''-morpholinyl)doxorubicin, a more potent experimental antitumor agent than doxorubicin, at 10(-8) M inhibited the Ca2+-dependent action potential by 22%, similar to the inhibition previously reported for doxorubicin. None of the agents affected the cell transmembrane potential, which suggests a lack of an effect on the mechanisms responsible for maintaining the resting cell membrane potential difference. The effects of the agents on the Ca2+-dependent action potential might reflect a direct effect on a plasma membrane Ca2+ channel or on the lipid domain around the channels, or they might be produced by changes in intracellular Ca2+ homeostasis, among other mechanisms. It is not known whether a change in the membrane Ca2+ current is related to the antitumor effects of the agents, but such a change may contribute to the neurotoxicity of cis-PDD and vincristine and the cardiac toxicity of the anthracycline.
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PMID:Effect of some anticancer drugs on the surface membrane electrical properties of differentiated murine neuroblastoma cells. 347 43

The effects of phorbol esters on Ca2+ channel currents in human neuroblastoma SH-SY5Y cells were studied using whole-cell patch-clamp recordings. Bath application of 12-O-tetradecanoylphorbol-13-acetate (TPA) or phorbol 12,13-dibutyrate (PDBu; 100 nM to 1 microM), known activators of protein kinase C (PKC), enhanced Ca2+ channel currents in a voltage-dependent manner similar to that of Bay K 8644. TPA also enhanced Ca2+ channel currents during cell dialysis with the PKC pseudosubstrate, PKC(19-36), and in cells which had been pre-incubated with 500 nM staurosporine, and which were exposed to staurosporine during recordings. Application of 4 alpha-phorbol-12,13-didecanoate (4 alpha-PDD; 100 nM), which does not activate PKC, caused current enhancement similar to the effects of TPA. However, intracellular dialysis of TPA was without effect on Ca2+ channel currents. Residual Ca2+ channel currents recorded after exposure to 1 microM omega-conotoxin GVIA were still enhanced by TPA, but in the presence of either Bay K 8644 (5 microM) or nifedipine (5 microM), TPA was without effect. When cells were pre-incubated for 10 min at 37 degrees C with 100 nM TPA, currents subsequently recorded in its absence were enhanced as compared to untreated cells; 5 microM nifedipine still inhibited currents to the same degree. This enhancement was not mimicked by 4 alpha-PDD, and was inhibited by staurosporine. Our results indicate that acute applications of phorbol esters (at concentrations commonly used to activate PKC) enhance L-type Ca2+ channel currents in SH-SY5Y cells via a PKC-independent mechanism which appears similar to that induced by Bay K 8644. By contrast, pre-incubation with TPA enhances both L- and N-type currents via activation of PKC.
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PMID:Enhancement of Ca2+ channel currents in human neuroblastoma (SH-SY5Y) cells by phorbol esters with and without activation of protein kinase C. 754 Jul 48

Expansion of the natural killer (NK) subset of lymphocytes represents a rare leukemia phenotype with variations in clinical presentation, morphology, surface phenotype, and effector function. This paper reports on a 5-year-old male patient who had an unusual presentation of an NK cell leukemia that was initially diagnosed as neuroblastoma. A bone marrow (BM) aspirate showed clumps of undifferentiated cells with the following phenotype: CD56bright+, CD33dim+, CD45-, CD2-, CD19-, CD16-, and CD57-. Cytochemistry was noncontributory. The patient, having failed to respond to conventional neuroblastoma chemotherapy, was subsequently diagnosed as having NK cell leukemia based on functional in vitro assays. The patient responded to acute lymphoblastic leukemia (ALL) chemotherapy but relapsed 4 weeks into treatment and eventually died 25 weeks after initial presentation. The cell surface phenotype observed is consistent with a rare NK cell subset, the biology of which has not been well defined. Freshly isolated BM cells killed K562 cells in a conventional 51Cr-release assay. Both interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) induced LAK activity against the Daudi cell line. IL-2 induced proliferation of the leukemic cells. TNF-alpha, IFN-gamma, IL-6, IL-1ra, and TGF-beta levels were assessed and found to be concentrated in BM, in contrast to plasma samples. TNF-alpha was present at a high concentration in BM (150.9 pg/ml), probably a reflection of the associated disease pathology of severe bone pain and pyrexia. In summary, this paper details clinical and laboratory investigations of a leukemia of a rare NK cell subset.
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PMID:Recognition of unusual presentation of natural killer cell leukemia. 757 92

Osteogenic protein-1 (OP-1) is a member of the TGF-beta superfamily that is expressed in the nervous system. We recently showed that human recombinant osteogenic protein-1 (hOP-1) strongly promotes the aggregation of dividing neuroblastoma x glioma hybrid NG108-15 cells, in part by inducing the major isoforms of the neural cell adhesion molecule (N-CAM) (Perides, G., Safran, R. M., Rueger, D. C., and Charness, M. E. (1992) Proc. Natl. Acad. Sci. U. S. A. 89, 10326-10330). Here we show that hOP-1 induces L1 expression approximately 6-fold in NG108-15 cells without changing the levels of N-cadherin, neurofilament 200, Thy-1, tau, and G alpha s. OP-1 induction of L1 and N-CAM was unassociated with changes in cell proliferation and was not reproduced by cellular differentiation. The increased adhesiveness of hOP-1-treated NG108-15 cells could be inhibited in part by Fab fragments of an anti-L1 polyclonal antiserum. L1 and N-CAM expression first increased 12-18 h after hOP-1 treatment, reached a maximum after 2-3 days, persisted for up to 5 days, and returned to control levels 3 days after hOP-1 withdrawal. The increases in L1 and N-CAM protein levels were preceded or accompanied by large increases in the abundance of L1 and all detectable N-CAM mRNAs. Actinomycin D prevented the induction by hOP-1 of L1 and N-CAM mRNAs, suggesting that hOP-1 regulates immunoglobulin CAM gene transcription. OP-1 is the first described growth factor that regulates both N-CAM and L1 gene expression.
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PMID:Osteogenic protein-1 regulates L1 and neural cell adhesion molecule gene expression in neural cells. 822 84

The C6 glial cell line has been used as a model cell system for the investigation of new glial produced neurotrophic and neurotropic molecules. By using the C6 cell line grown in a defined medium on collagen, this laboratory has isolated a distinct neurite promoting factor (NPF) that is potentiated by the presence of collagen (CPNPF). We have observed that C6 cells cultured in a defined medium on collagen (rat type-I) slowed their growth rate and expressed an astrocytic- or oligodendrocytic-like morphology. CPNPF, at this state of purity, appears to be a distinct NPF which induces neurite outgrowth (neurites of 1 or more somal diameters) in PC12 cells. These neurite promotion effects, however, appear to support the neuron morphology for only a short period (4 days) of time without the presence of neurotrophic factor (NTF). The neurite promoting activity is ineffective in inducing neurite outgrowth using mouse neuroblastoma cells (neuro-2a). CPNPF appears to be a heat stable protein whose activity does not depend on the presence of intact collagen, heparin sulfate proteoglycan (HSPG), or chondroitin sulfate proteoglycan (CSPG). Exposure to dissociative conditions results in a loss of neurite promoting activity. CPNPF is not a glycoprotein that contains an accessible alpha-D-mannopyranosyl, alpha-D-glucopyranosyl, or a sterically related residue (hydroxyl groups in the C-3,4, and 5 positions). Although these residues are not present on all glycoproteins, it does indicate that CPNPF is most likely not a glycoprotein. CPNPF activity is not blocked by neutralizing antibodies directed toward NGF, beta-FGF, IL-1 beta, IL-6, TGF-beta 2, TGF-beta 1.2, TGF-beta 3, TGF-beta 5, or EGF. CPNPF appears to either be oligomeric protein or a complex of proteins. On the basis of indirect evidence, it does not appear to be glial derived protease nexin-I. The alteration in morphology of the C6 glial cell line by serum-free conditions in the presence of collagen may have induced the production of a potentially new NPF not seen by previous investigators.
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PMID:Identification of a collagen potentiated neurite promoting factor isolated from C6 glioma cells. 836 Sep 47

The transforming growth factor (TGF)-betas are a highly conserved group of potent multifunctional cell regulatory proteins with variable effects on cell growth and differentiation. Most of the small round cell group of childhood tumors are thought to arise from either primitive mesenchyme or neuroectoderm and show evidence of skeletal muscle or neural differentiation, and rarely both. To investigate the possibility that the TGF-betas have a role in the growth or differentiation of these neoplasms, we used antibodies specific for peptide sequences of the three known mammalian TGF-beta isoforms (TGF-betas 1, 2, and 3) to probe for TGF-beta protein expression in a total of 49 cases. TGF-beta 1 immunoreactivity was present in 16/17 (94%) of rhabdomyosarcomas, and the staining intensity was usually strong. TGF-beta 1 was also present in three of three ectomesenchymomas. In contrast, TGF-beta 1 was absent in all but one out of nine poorly differentiated neuroblastomas. Differentiating neuronal cells of ganglioneuroblastomas, however, were strongly positive for TGF-beta 1. Ewing's sarcomas and peripheral primitive neuroectodermal tumors had a less consistent, but usually positive, staining pattern. TGF-beta 3 staining patterns were very similar to those of TGF-beta 1. TGF-beta 2 immunoreactivity was only rarely detected in this group of tumors. The results suggest different roles for TGF-betas 1 and 3 in neuroblastoma and rhabdomyosarcoma. Expression of TGF-betas 1 and 3 is associated with neuronal differentiation of neuroblastoma. In contrast, these proteins may promote the growth of rhabdomyosarcoma by suppressing differentiation.
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PMID:Expression of transforming growth factor-beta isoforms in small round cell tumors of childhood. An immunohistochemical study. 838 Sep 55

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